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The endothelial protein PLVAP in lymphatics controls the entry of lymphocytes and antigens into lymph nodes
Abstract
In the lymphatic sinuses of draining lymph nodes, soluble lymph-borne antigens enter the reticular conduits in a size-selective manner and lymphocytes transmigrate to the parenchyma. The molecular mechanisms that control these processes are unknown. Here we unexpectedly found that PLVAP, a prototypic endothelial protein of blood vessels, was synthesized in the sinus-lining lymphatic endothelial cells covering the distal conduits. In PLVAP-deficient mice, both small antigens and large antigens entered the conduit system, and the transmigration of lymphocytes through the sinus floor was augmented. Mechanistically, the filtering function of the lymphatic sinus endothelium was dependent on diaphragms formed by PLVAP fibrils in transendothelial channels. Thus, in the lymphatic sinus, PLVAP forms a physical sieve that regulates the parenchymal entry of lymphocytes and soluble antigens.
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“SCS floor LECs participate in the transport of soluble antigens into the lymph node parenchyma both through the process of receptor-independent antigen transcytosis and through their function as guardians of proteinaceous diaphragms present in the SCS floor through which antigens gain access to a collagenous reticular conduit system (124, 125).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [125]
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Metadata
- Authors
- Rantakari, P., Auvinen, K., Jäppinen, N., Kapraali, M., Valtonen, J., Karikoski, M., Gerke, H., Iftakhar-E-Khuda, I., Keuschnigg, J., Umemoto, E., Tohya, K., Miyasaka, M., Elima, K., Jalkanen, S., & Salmi, M.
- Affiliations
- University of Turku (FI)
- Immunology Frontier Research Center, The University of Osaka (JP)
- Kansai University of Health Sciences (JP)
- Corresponding author
- Salmi, Marko
- ORCID
- Venue
- Nature Immunology
- Published
- 2015-02-09
- Volume
- 16
- Issue
- 4
- Pages
- 386-396
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W1977274736
- Cited by
- 203
- References
- 51
- Citations by year
- 2026: 7 · 2025: 17 · 2024: 17 · 2023: 13 · 2022: 9 · 2021: 24 · 2020: 27 · 2019: 26 · 2018: 20 · 2017: 10 · 2016: 24 · 2015: 9
- FWCI
- 9.17
- Type
- journal article
- Language
- en
- Update notices
- erratum (2015-04-21)
- Open access
- closed
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science
- Topics
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
- Keywords
- PLVAP, lymphatic endothelium, lymph nodes, lymphatic sinuses, lymphocyte transmigration, size-selective filtration
- MeSH terms
- Animals, Antigens, Carrier Proteins, Endothelium, Lymphatic, Female, Gene Expression Regulation, Lymph Nodes, Lymphocytes, Male, Membrane Proteins, Mice, Inbred BALB C, Mice, Inbred C57BL, Signal Transduction, Antigens, CD, Mice, Knockout, Lymphatic Vessels, Endothelial Cells, Caveolin 1, Mice, Transendothelial and Transepithelial Migration
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